Sex differences in LDL-C reduction response to evolocumab: A propensity score matching analysis

Pharmacotherapy. 2024 Nov;44(11):861-869. doi: 10.1002/phar.4619. Epub 2024 Oct 23.

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the efficacy of evolocumab remain unclear. This study aimed to investigate sex differences in the efficacy of evolocumab using real-world data.

Method: Data were collected from the First Affiliated Hospital of Guangxi Medical University. A total of 416 eligible patients were selected from 1463 patients treated with evolocumab for secondary prevention. Clinical data, including individual characteristics and lipids profiles, were recorded. Propensity score matching (PSM) was used to control for potential confounders, with covariates including age, body mass index, smoking status, and diabetes. All eligible participants were propensity-matched 1:1 for female versus male with a match tolerance of 0.02. The efficacy of evolocumab in females and males was compared by PSM-adjusted analysis.

Results: In the PSM analysis, a significant difference was found in the relative percentage reduction of LDL-C between females and males (-42.7% vs. -54.4%, p < 0.001). In addition, the absolute LDL-C reduction was lower in females compared to males (interquartile range: -1.5 [-2.2, -0.8] mmol/L vs. -1.9 [-2.5, -1.0] mmol/L, p = 0.018). The rate of target LDL-C attainment was lower in females than in males after treatment with evolocumab (21.6% vs. 39.8%, p = 0.009).

Conclusion: These results suggest that males have a better response to evolocumab in term of LDL-C reduction compared to females.

Keywords: LDL‐C; PCSK9i; cardiovascular risk; evolocumab; sex differences.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Anticholesteremic Agents* / therapeutic use
  • Cholesterol, LDL* / blood
  • Female
  • Humans
  • Hypercholesterolemia / drug therapy
  • Male
  • Middle Aged
  • PCSK9 Inhibitors / therapeutic use
  • Propensity Score*
  • Proprotein Convertase 9
  • Retrospective Studies
  • Secondary Prevention / methods
  • Sex Characteristics
  • Sex Factors
  • Treatment Outcome

Substances

  • evolocumab
  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Anticholesteremic Agents
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9